Nitric oxide deficiency contributes to impairment of airway relaxation in cystic fibrosis mice

The pulmonary disease of cystic fibrosis (CF) is characterized by persisten t airway obstruction, which has been attributed to chronic endobronchial in fection and inflammation. The levels of exhaled nitric oxide (NO) are reduc ed in CF patients, which could contribute to bronchial obstruction through dysregulated constriction of airway smooth muscle, Because airway epitheliu m from CF mice has been shown to have reduced expression of inducible NO sy nthase, we examined airway responsiveness and relaxation in isolated trache as of CF mice. Airway relaxation as measured by percent relaxation of preco ntracted tracheal segments to electrical field stimulation (EFS) and substa nce P, a nonadrenergic, noncholinergic substance, was significantly impaire d in CF mice. The airway relaxation in response to prostaglandin E-2 was Si milar in CF and non-CF animals, Treatment with the NO synthase inhibitor NG -nitro-L-arginine methylester reduced tracheal relaxation induced by EFS in wild-type animals but had virtually no effect in the CF mice, Conversely, exogenous NO and L-arginine, a NO substrate, reversed the relaxation defect in CF airway. We conclude that the relative absence of NO compromises airw ays relaxation in CF, and may contribute to the bronchial obstruction seen in the disease.